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31. Apoptosis and apoptosis-related proteins (Fas, Fas ligand, Blc-2, p53) in lymphoid elements of human ovarian tumors

Author

Ben-Hur H, Gurevich P, Huszar M, Ben-Arie A, Berman V, Yevgeny Tendler, Zinder O, Tchanishev R, Gershon S, Mor G, Zaltsman Y, Kohen F, and Zusman I

Subjects
Ovarian Neoplasms, Lymphocytes, Tumor-Infiltrating, Proto-Oncogene Proteins c-bcl-2, CD8 Antigens, CD4 Antigens, Disease Progression, Humans, Apoptosis, Female, fas Receptor, Adenocarcinoma, Tumor Suppressor Protein p53, Ligands
Abstract

Different types of lymphocytes have different roles in tumor suppression. Thus, their expression of apoptosis-related proteins (ARP - Fas and Fas ligand, bcl-2, p53) in lymphocytes and their apoptosis were analyzed immunohistochemically in ovarian tumors of different grades. Ovaries without oncologic disorders had few lymphocytes, mainly T cells, and no ARP. Benign cysts presented features of weak immune reaction: small lymphoid infiltration and few lymphocytes. The ARP were present in 13.7% to 23.5% of the lymphocytes, and apoptosis was rare. In borderline tumors, expansion of lymphoid infiltrates and increased density of lymphocytes resulted in a tenfold rise in total lymphocytes, reflecting intensification of the immune response. Most lymphocytes were T cells (92%) predominated by CD8+ cells that were in direct contact with tumor epithelial cells. ARP species were found in 47% to 65% of the lymphocytes, and apoptosis in 2.2%. In carcinomas with ligh lymphoid infiltration, lymphocytes were 2.5 times more abundant, and the apoptotic index as well as the number of CD20+ and CD25+ lymphocytes rose sharply, whereas bcl-2 positive lymphocytes decreased to 8% of their number in borderline tumors. In carcinomas with low lymphoid infiltration, the total lymphocyte count decreased eightfold compared to carcinomas with high lymphoid infiltration, reflecting the deep subcompensation of the lymphoid system. Few p53-positive lymphocytes were found in the carcinomas. In conclusion, we found a positive correlation between apoptosis and the numbers of CD4+ or CD8+ lymphocytes in epithelial ovarian tumors. This correlation could reflect the antitumor activity of T cells. However, the high expression of ARP studied by immune cells at the vicinity of the tumor ARP reveals the lymphoid vulnerability to apoptosis, resulting in devastation of the lymphoid tissue, and consequently in tumor progression.

Published
2000

38. Membranal effects of phytoestrogens and carboxy derivatives of phytoestrogens on human vascular and bone cells: New insights based on studies with carboxy-biochanin A

Author

Somjen, D., primary, Kohen, F., additional, Lieberherr, M., additional, Gayer, B., additional, Schejter, E., additional, Katzburg, S., additional, Limor, R., additional, Sharon, O., additional, Knoll, E., additional, Posner, G.H., additional, Kaye, A.M., additional, and Stern, N., additional

Published
2005
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43. Synaptic remodeling in the arcuate nucleus during the estrous cycle is induced by estrogen and precedes the preovulatory gonadotropin surge

Author

Naftolin, F., Mor, G., Horvath, T. L., Luquin, S., Fajer, A. B., Kohen, F., García-Segura, Luis M., Naftolin, F., Mor, G., Horvath, T. L., Luquin, S., Fajer, A. B., Kohen, F., and García-Segura, Luis M.

Abstract

We have shown that the ovarian cycle is accompanied by a fall in the axosomatic synapses on randomly selected neurons of the arcuate nucleus by the morning of estrus, with a return to the preovulatory levels by the morning of metestrus, indicating a possible role in positive feedback. However, it remains to be proven that the circulating estradiol is the actual regulator of this physiological synaptic plasticity, or that estrogen- induced synaptic retraction precedes in the surge of gonadotropins at midcycle. To resolve these questions, we used an estradiol- immunoneutralization protocol and studied arcuate nucleus axosomatic synapses during the critical points of the estrous cycle. In addition to blocking positive feedback, estrogen immunoneutralization abolished synaptic retraction in the arcuate nucleus. As a positive control, the nonbinding estrogen diethylstilbestrol maintained the gonadotropin surge and synaptic retraction in the anti-estradiol-treated animals. Furthermore, in the diluent-treated cycling control females, the synaptic retraction was found to precede the preovulatory LH surge. We demonstrated that the midcycle synaptic retraction of arcuate nucleus synapses is induced by the preovulatory estradiol surge, and that these morphological events precede the preovulatory gonadotropin surge. Taken together, these observations strongly suggest that the hypothalamic mechanism underlying the physiological disinhibition of gonadotropins at midcycle (positive feedback) requires estrogen-induced synaptic retraction in the arcuate nucleus.

Published
1996

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